Predicting Antibody and ACE2 Affinity for SARS-CoV-2 BA.2.86 and JN.1 withIn SilicoProtein Modeling and Docking DOI Creative Commons
Shirish Yasa, Sayal Guirales-Medrano, Denis Jacob Machado

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 23, 2023

The emergence of SARS-CoV-2 lineages derived from Omicron, including BA.2.86 (nicknamed “Pirola”) and its relative, JN.1, has raised concerns about their potential impact on public personal health due to numerous novel mutations. Despite this, predicting implications based solely mutation counts proves challenging. Empirical evidence JN.1’s increased immune evasion capacity in relation previous variants is mixed. To improve predictions beyond what possible counts, we conducted extensive silico analyses the binding affinity between RBD different (Wuhan-Hu-1, BA.1/B.1.1.529, BA.2, XBB.1.5, BA.2.86, JN.1) neutralizing antibodies vaccinated or infected individuals, as well human angiotensin-converting enzyme 2 (ACE2) receptor. We observed no statistically significant difference JN.1 other variants. Therefore, conclude that new have pronounced escape infection compared However, minor reductions for both ACE2 were noted JN.1. discuss findings highlight need modeling docking studies go above basic serological neutralization analysis. Future research this area will benefit structural memory B-cell should emphasize importance choosing appropriate samples assess protection provided by vaccination infection. More-over, fitness benefits genomic variation outside be investigated. This contributes understanding variants’ health. Taken together, work introduces a paradigm functional epidemiology ongoing efforts combat evolving pandemic prepare hazards.

Language: Английский

Evolution of the SARS-CoV-2 Omicron spike DOI Creative Commons
Ruth Parsons, Priyamvada Acharya

Cell Reports, Journal Year: 2023, Volume and Issue: 42(12), P. 113444 - 113444

Published: Nov. 18, 2023

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant of concern, first identified in November 2021, rapidly spread worldwide and diversified into several subvariants. spike (S) protein accumulated an unprecedented number sequence changes relative to previous variants. In this review, we discuss how S structural features modulate host cell receptor binding, virus entry, immune evasion highlight these differentiate from We also examine key properties track across the still-evolving subvariants importance continuing surveillance evolution over time.

Language: Английский

Citations

35
Antigenic evolution of SARS coronavirus 2 DOI Creative Commons
Anna Z. Mykytyn, Ron A. M. Fouchier, Bart L. Haagmans

et al.

Current Opinion in Virology, Journal Year: 2023, Volume and Issue: 62, P. 101349 - 101349

Published: Aug. 28, 2023

SARS coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, emerged in China December 2019. Vaccines developed were very effective initially, however, virus has shown remarkable evolution with multiple variants spreading globally over last three years. Nowadays, newly emerging Omicron lineages are gaining substitutions at a fast rate, resulting escape from neutralization by antibodies that target Spike protein. Tools to map impact on further antigenic SARS-CoV-2, such as cartography, may be helpful update SARS-CoV-2 vaccines. In this review, we focus highlighting protein individually and combination immune escape.

Language: Английский

Citations

26
Altered receptor binding, antibody evasion and retention of T cell recognition by the SARS-CoV-2 XBB.1.5 spike protein DOI Creative Commons
Dhiraj Mannar, James W. Saville,

Chad Poloni

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Feb. 29, 2024

Abstract The XBB.1.5 variant of SARS-CoV-2 has rapidly achieved global dominance and exhibits a high growth advantage over previous variants. Preliminary reports suggest that the success stems from mutations within its spike glycoprotein, causing immune evasion enhanced receptor binding. We present binding studies demonstrate retention contacts with human ACE2 striking decrease in to mouse due revertant R493Q mutation. Despite extensive antibody binding, we highlight region on protein domain (RBD) is recognized by serum antibodies donor hybrid immunity, collected prior emergence variant. T cell assays reveal frequencies spike-specific CD4 + CD8 cells amongst donors skewed towards Th1 phenotype having attenuated effector cytokine secretion as compared ancestral protein-specific cells. Thus, while retained efficient gained antigenic alterations, it remains susceptible recognition induced via vaccination infection.

Language: Английский

Citations

10
ACE2-using merbecoviruses: Further evidence of convergent evolution of ACE2 recognition by NeoCoV and other MERS-CoV related viruses DOI Creative Commons
Qing Xiong,

Chengbao Ma,

Chen Liu

et al.

Cell Insight, Journal Year: 2024, Volume and Issue: 3(1), P. 100145 - 100145

Published: Jan. 30, 2024

Angiotensin-converting enzyme 2 (ACE2) was recognized as an entry receptor shared by coronaviruses from

Language: Английский

Citations

5
Determinants of species-specific utilization of ACE2 by human and animal coronaviruses DOI Creative Commons
Qingxing Wang, Sabrina Noettger,

Qinya Xie

et al.

Communications Biology, Journal Year: 2023, Volume and Issue: 6(1)

Published: Oct. 17, 2023

Utilization of human ACE2 allowed several bat coronaviruses (CoVs), including the causative agent COVID-19, to infect humans directly or via intermediate hosts. However, determinants species-specific differences in usage and frequency ability animal CoVs use are poorly understood. Here we applied VSV pseudoviruses analyze Spike proteins from 26 receptors across nine reservoir, potential We show that SARS-CoV-2 Omicron variants evolved towards more efficient but mutation R493Q BA.4/5 XBB disrupts utilization Greater horseshoe bats. Variations residues 31, 41 354 govern by coronaviral proteins. Mutation T403R allows RaTG13 CoV efficiently all orthologs for viral entry. Sera COVID-19 vaccinated individuals neutralize various Sarbecoviruses. Our results define receptor diverse suggest vaccination may protect against future zoonoses coronaviruses.

Language: Английский

Citations

11
Deciphering the free energy landscapes of SARS-CoV-2 wild type and Omicron variant interacting with human ACE2 DOI Open Access
Pham Dang Lan, Daniel A. Nissley, Edward P. O’Brien

et al.

The Journal of Chemical Physics, Journal Year: 2024, Volume and Issue: 160(5)

Published: Feb. 2, 2024

The binding of the receptor domain (RBD) SARS-CoV-2 spike protein to host cell angiotensin-converting enzyme 2 (ACE2) is first step in human viral infection. Therefore, understanding mechanism interaction between RBD and ACE2 at molecular level critical for prevention COVID-19, as more variants concern, such Omicron, appear. Recently, atomic force microscopy has been applied characterize free energy landscape RBD-ACE2 complex, including estimation distance transition state bound state, xu. Here, using a coarse-grained model replica-exchange umbrella sampling, we studied both wild type Omicron subvariants BA.1 XBB.1.5 interacting with ACE2. In agreement experiment, find that have similar xu values, but binds strongly than type, having lower dissociation constant KD.

Language: Английский

Citations

3
Predicting antibody and ACE2 affinity for SARS-CoV-2 BA.2.86 and JN.1 with in silico protein modeling and docking DOI Creative Commons
Shirish Yasa, Sayal Guirales-Medrano, Denis Jacob Machado

et al.

Frontiers in Virology, Journal Year: 2024, Volume and Issue: 4

Published: July 19, 2024

The emergence of SARS-CoV-2 lineages derived from Omicron, including BA.2.86 (nicknamed “Pirola”) and its relative, JN.1, has raised concerns about their potential impact on public personal health due to numerous novel mutations. Despite this, predicting implications based solely mutation counts proves challenging. Empirical evidence JN.1’s increased immune evasion capacity in relation previous variants is mixed. To improve predictions beyond what possible counts, we conducted extensive silico analyses the binding affinity between RBD different (Wuhan-Hu-1, BA.1/B.1.1.529, BA.2, XBB.1.5, BA.2.86, JN.1) neutralizing antibodies vaccinated or infected individuals, as well human angiotensin-converting enzyme 2 (ACE2) receptor. We observed no statistically significant difference JN.1 other variants. Therefore, conclude that new have pronounced escape infection compared However, minor reductions for both ACE2 were noted JN.1. Future research this area will benefit structural memory B-cell should emphasize importance choosing appropriate samples studies assess protection provided by vaccination infection. Moreover, fitness benefits genomic variation outside need be investigated. This contributes understanding variants’ health.

Language: Английский

Citations

2
Structural Basis for the Enhanced Infectivity and Immune Evasion of Omicron Subvariants DOI Creative Commons
Yaning Li, Yaping Shen, Yuanyuan Zhang

et al.

Viruses, Journal Year: 2023, Volume and Issue: 15(6), P. 1398 - 1398

Published: June 20, 2023

The Omicron variants of SARS-CoV-2 have emerged as the dominant strains worldwide, causing COVID-19 pandemic. Each subvariant contains at least 30 mutations on spike protein (S protein) compared to original wild-type (WT) strain. Here we report cryo-EM structures trimeric S proteins from BA.1, BA.2, BA.3, and BA.4/BA.5 subvariants, with BA.4 BA.5 sharing same mutations, each in complex surface receptor ACE2. All three receptor-binding domains BA.2 are "up", while BA.1 has two "up" one "down". BA.3 displays increased heterogeneity, majority all RBD state. different conformations preferences consistent their varied transmissibility. By analyzing position glycan modification Asn343, which is located S309 epitopes, uncovered underlying immune evasion mechanism subvariants. Our findings provide a molecular basis high infectivity thereby offering insights into potential therapeutic interventions against variants.

Language: Английский

Citations

6
Mechanistic study of the transmission pattern of the SARS‐CoV‐2 omicron variant DOI Creative Commons
Ke An,

Xianzhi Yang,

Mengqi Luo

et al.

Proteins Structure Function and Bioinformatics, Journal Year: 2024, Volume and Issue: 92(6), P. 705 - 719

Published: Jan. 5, 2024

Abstract The omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) characterized by 30 mutations in its spike protein, has rapidly spread worldwide since November 2021, significantly exacerbating the ongoing COVID‐19 pandemic. In order to investigate relationship between these and variant's high transmissibility, we conducted a systematic analysis mutational effect on spike–angiotensin‐converting enzyme‐2 (ACE2) interactions explored structural/energy correlation key mutations, utilizing reliable coarse‐grained model. Our study extended beyond receptor‐binding domain (RBD) trimer through comprehensive modeling full‐length rather than just RBD. free‐energy calculation revealed that enhanced binding affinity protein ACE2 receptor is correlated with increased structural stability isolated thus explaining heightened transmissibility. conclusion was supported our experimental analyses involving expression purification trimer. Furthermore, energy decomposition established those electrostatic make major contributions this effect. We categorized into four groups an analytical framework can be employed studying future mutations. Additionally, calculations rationalized reduced towards most available therapeutic neutralizing antibodies, when compared wild type. By providing concrete data offering solid explanation, contributes better understanding theories observations lays foundation for investigations.

Language: Английский

Citations

1
Engineering customized viral receptors for various coronaviruses DOI Creative Commons
Peng Liu, Meiling Huang, Hua Guo

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 4, 2024

Coronaviruses display versatile receptor usage, yet in-depth characterization of coronaviruses lacking known identities has been impeded by the absence feasible infection models. Here, we developed an innovative strategy to engineer functional customized viral receptors (CVRs). The modular design relies on building frameworks comprising various function modules and generating specific epitope-targeting binding domains. We showed key factors for CVRs efficiently facilitate spike cleavage, membrane fusion, pseudovirus entry, authentic virus amplification coronaviruses, resembling their native receptors. Applying this strategy, delineated accessible epitopes SARS-CoV-2 CVR elucidated mechanism entry supported amino-terminus domain (NTD) targeting S2L20-CVR. Furthermore, created CVR-expressing cells assessing antibodies inhibitors against 12 representative from six subgenera, most which Notably, a pan-sarbecovirus sarbecoviruses, as well replicable HKU3 strain RsHuB2019A. Through combining HKU5-specific with reverse genetics, successfully rescued cultured wild-type fluorescence protein-incorporated HKU5, receptor-unidentified merbecovirus. Our study demonstrated great potential in establishing receptor-independent models, paving way studying viruses that are challenging culture due lack susceptible cells.

Language: Английский

Citations

1